title: Histopathology of cryoballoon ablation-induced phrenic nerve injury.
abstract: BACKGROUND
  Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described.
  
  
  RESULTS
  A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups.
  
  
  CONCLUSIONS
  Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage.
authors.affiliation: Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Montreal, Canada.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Andrade
authors.forename: Marc
authors.initials: M
authors.lastname: Dubuc
authors.forename: Jose
authors.initials: J
authors.lastname: Ferreira
authors.forename: Peter G
authors.initials: PG
authors.lastname: Guerra
authors.forename: Evelyn
authors.initials: E
authors.lastname: Landry
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coulombe
authors.forename: Lena
authors.initials: L
authors.lastname: Rivard
authors.forename: Laurent
authors.initials: L
authors.lastname: Macle
authors.forename: Bernard
authors.initials: B
authors.lastname: Thibault
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.forename: Denis
authors.initials: D
authors.lastname: Roy
authors.forename: Paul
authors.initials: P
authors.lastname: Khairy
mesh_terms: D000818:Animals; D003452:Cryosurgery / Q000009:adverse effects*; D004285:Dogs; D061886:Neuromuscular Monitoring / Q000379:methods*; D059348:Peripheral Nerve Injuries / Q000209:etiology* / Q000473:pathology* / Q000517:prevention & control; D010791:Phrenic Nerve / Q000293:injuries* / Q000473:pathology*; D016896:Treatment Outcome
keywords: arrhythmia; atrial fibrillation; catheter ablation; complications; cryoballoon; pulmonary vein isolation; phrenic nerve